Synopsis: Retinoblastoma is a form of childhood cancer that starts from immature retinal cells in one or both of the persons eyes.

Main Document

Retinoblastoma is a rare form of tumor, accounting for approximately three-percent of all cancers in children under the age of fifteen.

Defining Retinoblastoma

Retinoblastoma is a form of childhood cancer that starts from immature retinal cells in one or both of the person's eyes and may begin from the time a child is still in the mother's womb until they are five years of age. The form of cancer is curable if it is caught early enough. Eighty-seven percent of children with this form of cancer around the world perish from it, most in developing nations. In developed countries, ninety-seven percent of children with retinoblastoma who survive live with moderate to severe visual impairments.

Retinoblastoma is a rare form of tumor, accounting for approximately three-percent of all cancers in children under the age of fifteen. The tumors start in the person's retina, which is the light-sensitive layer of the person's eye that enables them to see. Tumors that are present in one eye only are referred to as, 'unilateral retinoblastoma,' and when they are present in both of the person's eyes they are referred to as, 'bilateral retinoblastoma.' Nearly sixty-percent of the people who experience retinoblastoma have unilateral retinoblastoma, with the remainder experiencing bilateral retinoblastoma. Around ninety-percent of people with retinoblastoma do not have a family history of the disease; the remaining people who are newly diagnosed do have family members with retinoblastoma.

Each year in America it is estimated that approximately ten to fourteen million children between the ages of birth and four years of age experience retinoblastoma. While ninety-five percent of children with this form of cancer are diagnosed prior to age five, people with retinoblastoma who are diagnosed after the age of five tend to have a poorer diagnosis. Retinoblastoma is a tumor that occurs in both heritable and non-heritable forms. The heritable form of the disease includes people who have a positive family history, as well as those who have sustained a new mutation at the time of their conception. The fact that retinoblastoma is usually confined to the person's eye finds greater than ninety-percent of children with it being cured. The current challenge from a medical standpoint is treatment of retinoblastoma while preventing loss of the person's eye, blindness, or other serious effects as a result of treatment for the disease that may reduce the person's lifespan, or the quality of their life.

Causes of Retinoblastoma

The heritable form of retinoblastoma can manifest in either the unilateral or bilateral form of the disease. The majority of unilateral diseases are not heritable, although children with bilateral are presumed to have the inheritable form of the disease. Infants who have unilateral tumors are more likely to have the inheritable form of retinoblastoma, while older children with unilateral tumors are more likely to have the non-heritable form. Young children with unilateral tumors have fewer genetic abnormalities than older children. Children with the heritable form of retinoblastoma and have average eye examination results in at least one eye need to be re-examined frequently for the potential development of new tumors; approximately every two to four months for at least twenty-eight months. After receiving treatment, people with retinoblastoma require eye examinations until they reach age five.

'Trilateral,' retinoblastoma is a well-recognized syndrome consisting of either unilateral or bilateral heritable retinoblastoma in association with an intracranial neuroblastic tumor. Approximately five to fifteen percent of children with multi-focal, familial, or bilateral retinoblastoma might develop an intracranial neuroblastic tumor. Children who have the heritable form of retinoblastoma also have an increased risk of trilateral retinoblastoma, something that is associated with a poor prognosis. Intensive forms of therapy that are currently under development may offer some promise for children with this form of retinoblastoma.

Risks Related to Retinoblastoma

In a study of nine hundred and sixty-three people who were at least one year survivors of hereditary retinoblastoma in America between the years of 1914 and 1984, risks were elevated for soft tissue sarcoma overall, with leiomyosarcoma being the most frequent subtype, and seventy-eight percent of leiomyosarcomas diagnosed thirty or more years after the person received a diagnosis of retinoblastoma. The risks were elevated in people whether or not they were treated with radiation. In people who did receive radiation therapy, sarcomas were found both within and outside of the area of radiation treatment. What this suggests is that there may be a genetic predisposition to soft tissue sarcoma in some people.

There is a notable increase in mortality due to bladder, lung, and additional forms of epithelial cancers in people who have heritable retinoblastoma that did not receive radiation therapy. Tobacco use is something that is associated with these forms of cancers in this population. Carcinogenic effects of radiation increase with the dose administered, in particular for secondary sarcomas. In people who have received radiation therapy, two-thirds of the secondary cancers have occurred within the tissues that have been irradiated; one-third occurred outside of the irradiated tissues. The risks increase depending on the person's age at the time radiation therapy is administered, with the risk being less for people who are older than twelve months.

Symptoms of Retinoblastoma

Common signs of retinoblastoma include a white glow or glint in the pupil of one or both of the person's eyes in dim lighting, a white pupil in a color photograph, or crossed or misaligned eyes. If you notice a white glow in any of your children's pictures, contact a pediatrician or an ophthalmologist promptly and have their eyes examined. Ask them to dilate both of your child's eyes. If the doctor is unwilling or unable to dilate your child's eyes, seek another doctor.While it is rare, retinoblastoma may spread or, 'metastasize,' outside of a person's eye and into their brain, central nervous system, or bones. When this happens, chemotherapy is prescribed by a pediatrician who specializes in oncology, and is administered through the child's peripheral blood vessels, or into their brain for months or years after they are diagnosed.

Testing and Retinoblastoma

Siblings of people with retinoblastoma need to have regular ophthalmic exams. Studies suggest that DNA polymorphism analysis can assist in predicting who is at risk. Genetic counseling should be a part of the therapy a person with retinoblastoma receives, whether they have the unilateral or bilateral form of the disease. Ten to eighteen-percent of children with retinoblastoma have somatic genetic mosiacism, which makes their genetic, 'story,' more complex and contributes to the difficulty of genetic counseling.

Exon by exon sequencing of the person's RB1 gene demonstrates germline mutation in around ninety-percent of people with the heritable form of retinoblastoma. While a positive finding confirms susceptibility, a negative one does not rule it out. A multi-step assay includes DNA sequencing to identify mutations within coding exons and immediate flanking intronic regions, Southern blot analysis to characterize genomic rearrangements, and transcript analysis to characterize potential splicing mutations buried within introns. Expanded analysis shows promise in the ability to better define the functional significance of seemingly novel mutations in pilot investigations. The RB1 gene is located within the q14 band of chromosome 13. The absence of detectable RB1 mutations in some people might suggest that alternative genetic mechanisms could underlie the development of retinoblastoma.

Treatment of Retinoblastoma

The kind of treatment a person requires depends on the extent of the disease within their eye, as well as whether or not the disease has spread beyond their eye to their brain or other parts of their body. The risk of extraocular recurrence can be increased in the presence of pathologic sclera invasion, as well as in people who need bilateral enucleation. People who have retinoblastoma commonly have extensive disease in one eye at the time they are diagnosed, with either tumors that involve more than half of their retina, multiple tumors that are diffuse and involve their retina, or obvious seeding of the vitreous. People who have bilateral retinoblastoma should receive targeted, systemic therapy to treat the more severe eye. The goals of therapy involve eradication of the disease, preservation of the person's vision, as well as decreasing the risk of late sequelae from treatment.

People with retinoblastoma often experience a variety of long-term visual field defects after receiving treatment. The defects are related to the size of the tumor, its location, and the method of treatment administered. One study of visual acuity following treatment with systemic chemotherapy and focal ophthalmic therapy was conducted in forty children and involved fifty-four of their eyes. After a follow-up of sixty-eight months, twenty-seven of the children had a final visual acuity of 20/40 or better, while some children had eyes with a final visual acuity of 20/200 or better. The clinical factors that predicted visual acuity of 20/40 or better were a tumor margin of at least 3 millimeters from the foveola and optic disk, as well as an absence of sub-retinal fluid.

Systemic carboplatin is commonly used in the treatment of retinoblastoma. There has been some concern raised over hearing loss in relation to this form of therapy. A recent analysis of one hundred and sixty-four children who received treatment with six cycles of carboplatin-containing therapy demonstrated no loss of hearing among children who had an average initial audiogram.

People who are asymptomatic at the time they are diagnosed with an intracranial tumor tend to have a better overall survival rate than people who do experience symptoms. Screening through neuroimaging can improve their cure rate. One recommendation is that children with the heritable form of retinoblastoma should be screened using magnetic resonance neuroimaging, or CT scans, every six months after being diagnosed until they reach the age of five. Use of chemotherapy to reduce the extent of intraocular tumors in people with bilateral retinoblastoma could prevent development of pineal tumors.

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